Title of Invention

"A PROCESS FOR THE PREPARATION OF ESTER DERIVATIVES OF ACYCLIC MONOTERPENOID"

Abstract

The present invention relates to a process for the preparation of ester derivatives of acyclic monoterpenoids. The present invention particularly relates to a process for the synthesis 3,7-dimethyl-6-octen-l-ol (citronellal) and 3,7-diemthyl-2,6-octadien-l-ol (geraniol) esters by reacting these alcohol and C3-C5-mono-carboxylic acids in the presence of a lipase catalyst. These esters are used as flavour and perfumery chemicals in the cosmetic industry for manufact5uring the products of daily needs such as incense, dentifrice"s, perfumes, for flavouring confectionery, Pharmaceuticals, soap and dental preparations. The process steps are: reacting acyclic monoterpenoids such as herein described with C2-C5 mono carboxylic acid in the molar ratio of 1: 0.89 to 1:12 in presence of purified lipase catalyst, water at a temperature in the range of 25 to 35°C for a period of 4 to 6 hrs, stirring the reaction mixture, recovering the ester derivative from the reaction mixture by conventional methods using solvent.

Full Text

The present invention relates to a process for the preparation of ester derivatives of acyclic monoterpenoids. The present invention particularly relates to a process for the the synthesis 3,7-dimethyl-6-octen-l-ol (citronellol) and 3,7-dimethyl-2,6-octadien-l-ol (geraniol) esters by reacting these alcohol and C.^-C5-mono-carboxylic acids in the presence of a lipase catalyst. These esters are used as flavour and perfumery chemicals in the cosmetic industry for manufacturing the products of daily needs such as incense, dentifrice's, perfumes, for flavouring confectionery, Pharmaceuticals, soap and dental preparations. The synthesis of esters using similar starting materials are known in the literature. These reactions employed chemical estenfications and catalysts such as p-toluene sulphonic acid, metal alkylates etc. The products obtained through these type of reactions contain catalysts residues and bye-products, creating problems in purification. Contaminated esters are not suitable for use in the cosmetic applications. It is also affecting the olfactory property of the esters so produced. It is therefore desirable to prepare these esters without having any contamination. These esters may be prepared by enzymatic processes. But these processes suffer from disadvantages like low yield, high consumption of enzymes, difficulties in handling. Reference may be made to JAOCS 65(6), 1998, wherein it is reported that immobilized lipases were used for the synthesis of esters. The synthesis of esters involves the stirring a mixture of acid, alcohol (not citronellol and geraniol) in a reactor with lypase catalyst immobilized on acrylate resin, maintained at a temperature of 80°C. The water produced during the reaction was removed continuously by distilling off the water/alcohol mixture. The alcohol was charged to the reactor at the same rate at which it was distilled off. After 22 hr the reaction was complete and excess alcohol was removed from the mixture under reduced pressure to give the pure ester. The effect of water in these reactions is important because on the one hand the presence of water is required to avoid structural changes in the enzyme whereas on the other hand the absence of water is critical if a quantitative yield is required. Therefore the amount of water in the reaction system must be low, and the formed water must be removed from the reaction system continuously. The process is not so simple. In another reference (WO 88/02775, Ind Pat, 1990, 171813) it states that for the ester synthesis from short chain alcohols it is preferred to use Candida antactica lipase. The water removal was performed by azeotropic distillation of the mixture of water and the volatile alcohol under reduced pressure and at a temperature below 1800C. The process has limitation of using only C3-C4-alcohols specially secondary alcohols. For water removal vacuum was applied. In both the reports it was indicated the use of water removal from the reaction system. Reactions were carried out at high temperature and citronellol and geraniol as alcohols were not used According to the present invention the esterification of acyclic monoterpenoids such as 3,7-dimethyl-6-octen-l-ol (citronellol) and 3,7-dimethyl-2,6-octadien-l-ol (geraniol) and C2-C5-mono-carboxylic acid is conducted in such a way that water of reaction is maintained in such a level by suitably adjusting the amount of reactants. Suitable carboxylic acids in the practice of present invention are in particular straight chain mono-carboxyiic acids such as acetic acid, propionic acid, butyric acid, valeric acid. It is very important to canyout the esterification reaction under controlled and mild conditions because some of the reactants tend to form undesirable products. For the practice of this invention, suitable lipases are obtained from well known microorganism such as Candida species, Aspergillus niger, Pseudomonas species and are readily available from enzyme manufacturer. The main object of the present invention is to provide a process for the preparation of ester derivatives of acyclic monoterpenoids. Another object of the present invention is to provide a simple environment friendly enzymatic process for the synthesis 3,7-diemthyl-6-octen-l-ol (citronellol) and 3,7-diemthyl-2,6-octadien-l-ol (geraniol) esters, which obviates the drawbacks as detailed below. Accordingly, the present invention relates to a process for the preparation of ester derivatives of acyclic monoterpenoids which comprises; reacting acyclic monoterperiod such as herein described with C2-C5 mono carboxylic acid in the molar ratio of 1: 0.89 to 1:12 characteresed is that using purified lipase catalyst, water at a temperature in the range of 25 to 35 C for a period of 4 to 6 hrs, stirring the reaction mixture, recovering the ester derivative from the reaction mixture by conventional methods using solvent. In an embodiment of the present invention the carboxylic used may be selected from acetic, prop ionic, butyric or valeric acid. An another embodiment of the process is that the alcohol is 3,7-diemthyl-2,6-octadien-l-ol (geraniol) and the acid is acetic acid. In an another embodiment of the process the acid may be propionic acid or butyric acid and respective alcohols. In still another embodiment of the present invention the reaction may be carried out without using any organic solvent and preferably at a temperature in the range of 25 to 30°C. The different phases, through which the present process consists of, according to the present invention, are as follows: (a) Reaction of alcohol and acid in presence of lipase catalyst without using organic solvent (b) Processing of the reaction mixture (c) Purification of the product (d) Purification of the catalyst for recycles. (e) Analysis of the pure product. The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the present invention Example 1 3,7"dimethyl-6-octen-l-ol (citronellol) (0.2 ml) and acetic acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c). Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.2 g, yield 85%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained are tabulated in the following table (Table 1) (Table Removed) Example 2 3,7-dimethyl-6-octen-l-ol (citronellol) (0.2 ml) and propiomc acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c). Isolation of the ester: Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.178 g, yield 84%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained are tabulated in the following table (Table 2) (Table Removed) Example 3 Reaction : 3,7-dimethyl-6-octen-l-ol (citronellol) (0.2 ml) and butync acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c). Isolation of the ester: Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.197 g, yield 87%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98.5% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained ere tabulated in the following table (Table 3) (Table Removed) Example 4 Reaction : 3,7-dimethyl-6-octen-l-ol (citrnellol) (0.2 ml) and valeric acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cvclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (tic). Isolation of the ester: Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.212 g, yield 88%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained are tabulated in the following table (Table 4) (Table Removed) Example 5. 3,7-dimethyl-2,6-octadien-l-ol (geraniol) (0.2 ml) and acetic acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cydindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c). Isolation of the ester: Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml0 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.168 g, yield 84%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98% pure product. The same reaction was repeated in several expenments with variable parameters. The results so obtained ere tabulated in the following table (Table 5) (Table Removed) Example 6 Reaction : 3,7-dimethyl-2,6-octadien-l-ol (geramol) (0.2 ml) and propiomc acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c). Isolation of the ester : Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 mlO 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.178 g, yield 83%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98.5% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained ere tabulated in the following table (Table 6) (Table Removed) Example 7 Reaction : 3,7-dimethyl-2,6-octadien-l-ol (geraniol) (0.2 ml) and butyric acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromatography (t1c), Isolation of the ester: Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.193 g, yield 86%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98.5% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained ere tabulated in the following table (Table 7) (Table Removed) Example 8 Reaction : 3,7-dimethyl-2,6-octadien-l-ol (geramol) (0.2 ml) and valeric acid (0.1 ml) was taken in a 25 ml round bottom flask kept over a magnetic stirrer. To this lipase catalyst (Candida cyclindracea) (0.003 g, 100 u) and water (0.1 ml) were added and started stirring at 30°C for 4 hours. The reaction was monitored by thin layer chromat6graphy (t1c) Isolation of the ester : Water (0.2 ml) was added to the reaction mixture and extracted with diethyl ether (2 ml) 3 times. The ether extract was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure (20 mm of Hg) to give the ester, 0.207 g, yield 87%. The ester was analysed by Gas Liquid Chromatography (GLC) to give 98% pure product. The same reaction was repeated in several experiments with variable parameters. The results so obtained ere tabulated in the following table (Table 8) (Table Removed) The main advantages of the present invention are the followings : 1. The starting two alcohols, citronellol and geraniol are natural products 2. The reactions do not require any solvent during the process 3. The chemical reactions involved are environment friendly, because no toxic substances ere liberated as effluent which may pollute the environment. 4. The process is very simple and does not involve any sophisticated equipment for operation. 5. The product esters ere suitable for use directly in the user industry as they pass the specification 6. The catalyst may be reused after purification, reducing the cost of production. 7. The olfactory property of the product does not change due to the type of process used. 8 The Time taken for The entire process is short. We Claim: 1. A process for the preparation of ester derivatives of acyclic monoterpenoids which comprises; reacting acyclic monoterpenoids such as herein described with C2-C5 mono Charactaresed is that using carboxylic acid in the molar ratio of 1: 0.89 to 1:12 purified lipase catalyst, water at a temperature in the range of 25 to 35 C for a period of 4 to 6 hrs, stirring the reaction mixture, recovering the ester derivative from the reaction mixture by conventional methods using solvent.. 2. A process as claimed in claims 1 wherein the reaction is carried out preferably at 25 to 30°C. 3. A process as claimed in claims 1 to 2 wherein the reaction is carried out by magnetically stirrings. 4. A process as claimed in claims 1 to 3 wherein diethyl ether is used as solvent for extraction of the ester from the reaction mixture. 5. A process as claimed in claims 1 to 3 wherein the acyclic monoterpenoid used is selected from geraniol, citronellal. 6. A process for the preparation of ester derivatives of acyclic monoterpeniods substantially as herein described with reference to the examples.

Documents:

46-del-2001-abstract.pdf

46-del-2001-claims.pdf

46-del-2001-correspondence-others.pdf

46-del-2001-correspondence-po.pdf

46-del-2001-description (complete).pdf

46-del-2001-form-1.pdf

46-del-2001-form-19.pdf

46-del-2001-form-2.pdf

46-del-2001-form-3.pdf